Apoptosis in human liver carcinoma caused by gold nanoparticles in combination with carvedilol is mediated via modulation of MAPK/Akt/mTOR pathway and EGFR/FAAD proteins
| Autor: | Alan Chan, Luis J. Cruz, Heloiza F. O. Silva, Jonas Bispo Pessoa, Raimundo Fernandes de Araújo, Rômulo S. Cavalcante, Luiz H. S. Gasparotto, Aurigena Antunes de Araújo, Gerly Anne de Castro Brito, Paulo Marcos da Matta Guedes, Emilio de Castro Miguel |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Programmed cell death MAP Kinase Signaling System Carbazoles Metal Nanoparticles carvedilol Propanolamines 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Survivin Antineoplastic Combined Chemotherapy Protocols Humans cancer FADD Propidium iodide Protein kinase B PI3K/AKT/mTOR pathway combination biology TOR Serine-Threonine Kinases Liver Neoplasms apoptosis Hep G2 Cells Molecular biology 3. Good health ErbB Receptors Oxidative Stress 030104 developmental biology HEK293 Cells Oncology chemistry Apoptosis 030220 oncology & carcinogenesis gold nanoparticles biology.protein Gold Proto-Oncogene Proteins c-akt |
| Zdroj: | International Journal of Oncology International Journal of Oncology, 52(1), 189-200 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2017.4179 |
| Popis: | In cancers, apoptosis signaling pathways and cell survival and growth pathways responsible for resistance to conventional treatments, such as Pi3K/Akt/mTOR and mitogen-activated protein kinase (MAPK) become dysregulated. Recently, alternative treatments to promote tumor cell death have become important. The present study reports on the antitumor and cytoprotective action of gold nanoparticles (GNPs) and carvedilol in combination and in isolated application. Apoptosis was analyzed by FITC/propidium iodide staining flow cytometry; caspase-3, caspase-8, Bcl-2 and MAPK/ERK activity by immunofluorescence microscopy; gene expression of proteins related to cell death as Akt, mTOR, EGFR, MDR1, survivin, FADD and Apaf, by the real-time PCR; and western blot analysis for MAPK/ERK, Akt and mTOR. Oxidative stress evaluation was performed by reduced glutathione (GSH) and malondialdehyde (MDA) levels. Intracellular GNPs targets were identified by transmission electron microscopy. After exposure to a combination of GNPs (6.25 µg/ml) and carvedilol (3 µM), death as promoted by apoptosis was detected using flow cytometry, for expression of pro-apoptotic proteins FADD, caspase-3, caspase-8 and sub-regulation of anti-apoptotic MAPK/ERK, Akt, mTOR, EGFR and MDR1 resistance. Non-tumor cell cytoprotection with GSH elevation and MDA reduction levels was detected. GNPs were identified within the cell near to the nucleus when combined with carvedilol. The combination of GNP and carvedilol promoted downregulation of anti-apoptotic and drug resistance genes, over-regulation of pro-apoptotic proteins in tumor cells, as well as cytoprotection of non-tumor cells with reduction of apoptosis and oxidative stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|